An Experimenter’s Guide to Glioblastoma Invasion Pathways

Louis, 2016, The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary, Acta Neuropathol., 131, 803, 10.1007/s00401-016-1545-1 Stupp, 2009, Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial, Lancet Oncol., 10, 459, 10.1016/S1470-2045(09)70025-7 Prados, 2015, Toward precision medicine in glioblastoma: the promise and the challenges, Neuro Oncol., 17, 1051, 10.1093/neuonc/nov031 Kallenberg, 2013, Glioma infiltration of the corpus callosum: early signs detected by DTI, J. Neurooncol., 112, 217, 10.1007/s11060-013-1049-y Cheng, 2011, Elevated invasive potential of glioblastoma stem cells, Biochem. Biophys. Res. Commun., 406, 643, 10.1016/j.bbrc.2011.02.123 Bao, 2006, Glioma stem cells promote radioresistance by preferential activation of the DNA damage response, Nature, 444, 756, 10.1038/nature05236 Verhaak, 2010, Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1, Cancer Cell, 17, 98, 10.1016/j.ccr.2009.12.020 Phillips, 2006, Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis, Cancer Cell, 9, 157, 10.1016/j.ccr.2006.02.019 Segerman, 2016, Clonal variation in drug and radiation response among glioma-initiating cells is linked to proneural-mesenchymal transition, Cell Rep., 17, 2994, 10.1016/j.celrep.2016.11.056 Milano, 2010, Patterns and timing of recurrence after temozolomide-based chemoradiation for glioblastoma, Int. J. Radiat. Oncol. Biol. Phys., 78, 1147, 10.1016/j.ijrobp.2009.09.018 Lun, 2011, The natural history of extracranial metastasis from glioblastoma multiforme, J. Neurooncol., 105, 261, 10.1007/s11060-011-0575-8 Bellail, 2004, Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion, Int. J. Biochem. Cell Biol., 36, 1046, 10.1016/j.biocel.2004.01.013 Osswald, 2015, Brain tumour cells interconnect to a functional and resistant network, Nature, 528, 93, 10.1038/nature16071 Cuddapah, 2014, A neurocentric perspective on glioma invasion, Nat. Rev. Neurosci., 15, 455, 10.1038/nrn3765 Gritsenko, 2012, Interstitial guidance of cancer invasion, J. Pathol., 226, 185, 10.1002/path.3031 Rao, 2014, Toward 3D biomimetic models to understand the behavior of glioblastoma multiforme cells, Tissue Eng. B Rev., 20, 314, 10.1089/ten.teb.2013.0227 Lee, 2006, Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines, Cancer Cell, 9, 391, 10.1016/j.ccr.2006.03.030 Kania, 2016, Mechanisms of ephrin–Eph signalling in development, physiology and disease, Nat. Rev. Mol. Cell Biol., 17, 240, 10.1038/nrm.2015.16 Himanen, 2004, Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling, Nat. Neurosci., 7, 501, 10.1038/nn1237 Todd, 2017, EphA4 regulates neuroblast and astrocyte organization in a neurogenic niche, J. Neurosci., 37, 3331, 10.1523/JNEUROSCI.3738-16.2017 Jiao, 2008, Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system, Proc. Natl. Acad. Sci. U. S. A., 105, 8778, 10.1073/pnas.0708861105 Nakada, 2010, The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion, Int. J. Cancer, 126, 1155 Day, 2013, EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme, Cancer Cell, 23, 238, 10.1016/j.ccr.2013.01.007 Wang, 2008, Increased expression of EphA2 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients, Oncol. Rep., 19, 151 Wang, 2008, Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients, BMC Cancer, 8, 79, 10.1186/1471-2407-8-79 Binda, 2012, The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas, Cancer Cell, 22, 765, 10.1016/j.ccr.2012.11.005 Liu, 2006, A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma, Cancer Res., 66, 10815, 10.1158/0008-5472.CAN-06-1408 Miao, 2015, EphA2 promotes infiltrative invasion of glioma stem cells in vivo through cross-talk with Akt and regulates stem cell properties, Oncogene, 34, 558, 10.1038/onc.2013.590 Wykosky, 2005, EphA2 as a novel molecular marker and target in glioblastoma multiforme, Mol. Cancer Res., 3, 541, 10.1158/1541-7786.MCR-05-0056 Teng, 2013, Ligand-dependent EphB1 signaling suppresses glioma invasion and correlates with patient survival, Neuro Oncol., 15, 1710, 10.1093/neuonc/not128 Wang, 2012, EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase, Oncogene, 31, 5132, 10.1038/onc.2012.16 Nakada, 2004, The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells, Cancer Res., 64, 3179, 10.1158/0008-5472.CAN-03-3667 Tu, 2012, Expression of EphrinB2 and EphB4 in glioma tissues correlated to the progression of glioma and the prognosis of glioblastoma patients, Clin. Transl. Oncol., 14, 214, 10.1007/s12094-012-0786-2 Nakada, 2006, Ephrin-B3 ligand promotes glioma invasion through activation of Rac1, Cancer Res., 66, 8492, 10.1158/0008-5472.CAN-05-4211 Krusche, 2016, EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells, eLife, 5, 10.7554/eLife.14845 Hatano, 2005, EphA2 as a glioma-associated antigen: a novel target for glioma vaccines, Neoplasia, 7, 717, 10.1593/neo.05277 Li, 2009, EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor, Oncogene, 28, 1759, 10.1038/onc.2009.15 Day, 2014, Eph receptors as therapeutic targets in glioblastoma, Br. J. Cancer, 111, 1255, 10.1038/bjc.2014.73 Sahai, 2002, RHO-GTPases and cancer, Nat. Rev. Cancer, 2, 133, 10.1038/nrc725 Ridley, 2015, Rho GTPase signalling in cell migration, Curr. Opin. Cell Biol., 36, 103, 10.1016/j.ceb.2015.08.005 Fortin Ensign, 2013, Implications of Rho GTPase signaling in glioma cell invasion and tumor progression, Front. Oncol., 3, 241, 10.3389/fonc.2013.00241 Tran, 2006, Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome, Cancer Res., 66, 9535, 10.1158/0008-5472.CAN-06-0418 Chuang, 2004, Role of synaptojanin 2 in glioma cell migration and invasion, Cancer Res., 64, 8271, 10.1158/0008-5472.CAN-04-2097 Feng, 2011, Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFRα-stimulated glioma tumorigenesis in mice and humans, J. Clin. Invest., 121, 4670, 10.1172/JCI58559 Feng, 2014, EGFRvIII stimulates glioma growth and invasion through PKA-dependent serine phosphorylation of Dock180, Oncogene, 33, 2504, 10.1038/onc.2013.198 Fortin, 2012, Cdc42 and the guanine nucleotide exchange factors Ect2 and trio mediate Fn14-induced migration and invasion of glioblastoma cells, Mol. Cancer Res., 10, 958, 10.1158/1541-7786.MCR-11-0616 Hirata, 2012, In vivo fluorescence resonance energy transfer imaging reveals differential activation of Rho-family GTPases in glioblastoma cell invasion, J. Cell Sci., 125, 858, 10.1242/jcs.089995 Murray, 2014, Guanine nucleotide exchange factor Dock7 mediates HGF-induced glioblastoma cell invasion via Rac activation, Br. J. Cancer, 110, 1307, 10.1038/bjc.2014.39 Wang, 2014, Tax-interacting protein 1 coordinates the spatiotemporal activation of Rho GTPases and regulates the infiltrative growth of human glioblastoma, Oncogene, 33, 1558, 10.1038/onc.2013.97 Salhia, 2008, The guanine nucleotide exchange factors trio, Ect2, and Vav3 mediate the invasive behavior of glioblastoma, Am. J. Pathol., 173, 1828, 10.2353/ajpath.2008.080043 Kwiatkowska, 2012, The small GTPase RhoG mediates glioblastoma cell invasion, Mol. Cancer, 11, 65, 10.1186/1476-4598-11-65 Gont, 2017, PREX1 integrates G protein-coupled receptor and phosphoinositide 3-kinase signaling to promote glioblastoma invasion, Oncotarget, 8, 8559, 10.18632/oncotarget.14348 Tang, 2013, c-Src and neural Wiskott-Aldrich syndrome protein (N-WASP) promote low oxygen-induced accelerated brain invasion by gliomas, PLoS One, 8, 10.1371/journal.pone.0075436 Watanabe, 1999, Cooperation between mDia1 and ROCK in Rho-induced actin reorganization, Nat. Cell Biol., 1, 136, 10.1038/11056 Arden, 2015, Small-molecule agonists of mammalian Diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy, Mol. Biol. Cell, 26, 3704, 10.1091/mbc.e14-11-1502 Chesarone, 2010, Unleashing formins to remodel the actin and microtubule cytoskeletons, Nat. Rev. Mol. Cell Biol., 11, 62, 10.1038/nrm2816 Riento, 2003, Rocks: multifunctional kinases in cell behaviour, Nat. Rev. Mol. Cell Biol., 4, 446, 10.1038/nrm1128 Qin, 2017, Neural precursor-derived pleiotrophin mediates subventricular zone invasion by glioma, Cell, 170, 10.1016/j.cell.2017.07.016 Pencheva, 2017, Identification of a druggable pathway controlling glioblastoma invasiveness, Cell Rep., 20, 48, 10.1016/j.celrep.2017.06.036 Olsten, 2004, Order or chaos? An evaluation of the regulation of protein kinase CK2, Biochem. Cell Biol., 82, 681, 10.1139/o04-116 Ulrich, 2009, The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells, Cancer Res., 69, 4167, 10.1158/0008-5472.CAN-08-4859 Amodeo, 2017, A PML/Slit axis controls physiological cell migration and cancer invasion in the CNS, Cell Rep., 20, 411, 10.1016/j.celrep.2017.06.047 Scaglioni, 2006, A CK2-dependent mechanism for degradation of the PML tumor suppressor, Cell, 126, 269, 10.1016/j.cell.2006.05.041 Ji, 2013, The role of protein kinase CK2 in glioblastoma development, Clin. Cancer Res., 19, 6335, 10.1158/1078-0432.CCR-13-2478 Zheng, 2013, Targeting protein kinase CK2 suppresses prosurvival signaling pathways and growth of glioblastoma, Clin. Cancer Res., 19, 6484, 10.1158/1078-0432.CCR-13-0265 Parhar, 2007, The role of protein kinase CK2 in intestinal epithelial cell inflammatory signaling, Int. J. Colorectal Dis., 22, 601, 10.1007/s00384-006-0193-7 Friedmann-Morvinski, 2016, Targeting NF-kappaB in glioblastoma: a therapeutic approach, Sci. Adv., 2, 10.1126/sciadv.1501292 Cahill, 2016, Nuclear factor-kappaB in glioblastoma: insights into regulators and targeted therapy, Neuro Oncol., 18, 329, 10.1093/neuonc/nov265 Bhat, 2013, Mesenchymal differentiation mediated by NF-kappaB promotes radiation resistance in glioblastoma, Cancer Cell, 24, 331, 10.1016/j.ccr.2013.08.001 Lee, 2013, The NF-kappaB RelB protein is an oncogenic driver of mesenchymal glioma, PLoS One, 8 Dhruv, 2013, Reciprocal activation of transcription factors underlies the dichotomy between proliferation and invasion of glioma cells, PLoS One, 8, 10.1371/journal.pone.0072134 Channavajhala, 2002, Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis, Oncogene, 21, 5280, 10.1038/sj.onc.1205640 Zheng, 2014, JAK2/STAT3 targeted therapy suppresses tumor invasion via disruption of the EGFRvIII/JAK2/STAT3 axis and associated focal adhesion in EGFRvIII-expressing glioblastoma, Neuro Oncol., 16, 1229, 10.1093/neuonc/nou046 Carro, 2010, The transcriptional network for mesenchymal transformation of brain tumours, Nature, 463, 318, 10.1038/nature08712 Senft, 2011, Inhibition of the JAK-2/STAT3 signaling pathway impedes the migratory and invasive potential of human glioblastoma cells, J. Neurooncol., 101, 393, 10.1007/s11060-010-0273-y Priester, 2013, STAT3 silencing inhibits glioma single cell infiltration and tumor growth, Neuro Oncol., 15, 840, 10.1093/neuonc/not025 Gray, 2014, NF-kappaB and STAT3 in glioblastoma: therapeutic targets coming of age, Expert Rev. Neurother., 14, 1293, 10.1586/14737175.2014.964211 Kesanakurti, 2013, Essential role of cooperative NF-kappaB and Stat3 recruitment to ICAM-1 intronic consensus elements in the regulation of radiation-induced invasion and migration in glioma, Oncogene, 32, 5144, 10.1038/onc.2012.546 Zhang, 2011, Blockade of TGF-beta signaling by the TGFbetaR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma, Cancer Res., 71, 7155, 10.1158/0008-5472.CAN-11-1212 Reyes, 2013, alphavbeta8 integrin interacts with RhoGDI1 to regulate Rac1 and Cdc42 activation and drive glioblastoma cell invasion, Mol. Biol. Cell, 24, 474, 10.1091/mbc.e12-07-0521 Tchaicha, 2011, Glioblastoma angiogenesis and tumor cell invasiveness are differentially regulated by beta8 integrin, Cancer Res., 71, 6371, 10.1158/0008-5472.CAN-11-0991 Noren, 2004, Eph receptor–ephrin bidirectional signals that target Ras and Rho proteins, Cell. Signal., 16, 655, 10.1016/j.cellsig.2003.10.006 Nakada, 2005, EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion, Am. J. Pathol., 167, 565, 10.1016/S0002-9440(10)62998-7 Basu, 2018, Oncogenic RAS-induced perinuclear signaling complexes requiring KSR1 regulate signal transmission to downstream targets, Cancer Res., 78, 891, 10.1158/0008-5472.CAN-17-2353 Venkatesh, 2017, Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma, Nature, 549, 533, 10.1038/nature24014 Christina, 2004, Rac1 and PAK1 are upstream of IKK-ε and TBK-1 in the viral activation of interferon regulatory factor-3, FEBS Lett., 567, 230, 10.1016/j.febslet.2004.04.069 Gonzalez-Forero, 2012, Endogenous Rho-kinase signaling maintains synaptic strength by stabilizing the size of the readily releasable pool of synaptic vesicles, J. Neurosci., 32, 68, 10.1523/JNEUROSCI.3215-11.2012 Shin, 2013, Protein kinase CK2 phosphorylates and activates p21-activated kinase 1, Mol. Biol. Cell, 24, 2990, 10.1091/mbc.e13-04-0204 Herrmann, 2015, Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3γ, and Dok-7 proteins and phosphorylates the latter two, J. Biol. Chem., 290, 22370, 10.1074/jbc.M115.647610 Bryja, 2008, β-Arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways, EMBO Rep., 9, 1244, 10.1038/embor.2008.193 Kramerov, 2012, Cell rounding in cultured human astrocytes and vascular endothelial cells upon inhibition of CK2 is mediated by actomyosin cytoskeleton alterations, J. Cell. Biochem., 113, 2948, 10.1002/jcb.24171 Takeda, 2005, Phosphorylation of RanGAP1 stabilizes its interaction with Ran and RanBP1, Cell Struct. Funct., 30, 69, 10.1247/csf.30.69 Galovic, 2011, Interplay between N-WASP and CK2 optimizes clathrin-mediated endocytosis of EGFR, J. Cell Sci., 124, 2001, 10.1242/jcs.081182 Pocha, 2009, WAVE2 is regulated by multiple phosphorylation events within its VCA domain, Cell Motil. Cytoskelet., 66, 36, 10.1002/cm.20323 Apel, 1991, Phosphorylation of neuromodulin (GAP-43) by casein kinase II. Identification of phosphorylation sites and regulation by calmodulin, J. Biol. Chem., 266, 10544, 10.1016/S0021-9258(18)99258-6 Dokas, 1998, Regulation ofin vitro phosphorylation of the casein kinase II sites in B-50 (GAP-43), Brain Res., 781, 320, 10.1016/S0006-8993(97)01257-2 Golub, 2005, PI(4,5)P2-dependent microdomain assemblies capture microtubules to promote and control leading edge motility, J. Cell Biol., 169, 151, 10.1083/jcb.200407058 Matsuo, 2002, Characterization of STEF, a guanine nucleotide exchange factor for Rac1, required for neurite growth, J. Biol. Chem., 277, 2860, 10.1074/jbc.M106186200 Lakhe-Reddy, 2006, Beta8 integrin binds Rho GDP dissociation inhibitor-1 and activates Rac1 to inhibit mesangial cell myofibroblast differentiation, J. Biol. Chem., 281, 19688, 10.1074/jbc.M601110200 Lee, 2015, Protein tyrosine phosphatase-PEST and beta8 integrin regulate spatiotemporal patterns of RhoGDI1 activation in migrating cells, Mol. Cell. Biol., 35, 1401, 10.1128/MCB.00112-15 Cavin, 2003, Inhibition of CK2 activity by TGF-beta1 promotes IkappaB-alpha protein stabilization and apoptosis of immortalized hepatocytes, Hepatology, 38, 1540 Kim, 2013, CK2 inhibitor CX-4945 blocks TGF-beta1-induced epithelial-to-mesenchymal transition in A549 human lung adenocarcinoma cells, PLoS One, 8 Singh, 2006, Transforming growth factor-beta-induced expression of the apolipoprotein E gene requires c-Jun N-terminal kinase, p38 kinase, and casein kinase 2, Arterioscler. Thromb. Vasc. Biol., 26, 1323, 10.1161/01.ATV.0000220383.19192.55 Zdunek, 2001, Protein kinase CK2 mediates TGF-beta1-stimulated type IV collagen gene transcription and its reversal by estradiol, Kidney Int., 60, 2097, 10.1046/j.1523-1755.2001.00041.x van Tellingen, 2015, Overcoming the blood–brain tumor barrier for effective glioblastoma treatment, Drug Resist. Updat., 19, 1, 10.1016/j.drup.2015.02.002 Giannelli, 2014, Transforming growth factor-beta as a therapeutic target in hepatocellular carcinoma, Cancer Res., 74, 1890, 10.1158/0008-5472.CAN-14-0243 Brandes, 2016, A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma, Neuro Oncol., 18, 1146, 10.1093/neuonc/now009 Martiny-Baron, 2010, The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis, Angiogenesis, 13, 259, 10.1007/s10456-010-9183-z Sulzmaier, 2014, FAK in cancer: mechanistic findings and clinical applications, Nat. Rev. Cancer, 14, 598, 10.1038/nrc3792 Rath, 2018, Rho kinase inhibition by AT13148 blocks pancreatic ductal adenocarcinoma invasion and tumor growth, Cancer Res., 78, 3321, 10.1158/0008-5472.CAN-17-1339 Patel, 2012, RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer, Cancer Res., 72, 5025, 10.1158/0008-5472.CAN-12-0954 Griveau, 2018, A glial signature and Wnt7 signaling regulate glioma-vascular interactions and tumor microenvironment, Cancer Cell, 33, 10.1016/j.ccell.2018.03.020 Friedl, 2011, Cancer invasion and the microenvironment: plasticity and reciprocity, Cell, 147, 992, 10.1016/j.cell.2011.11.016 Zhong, 2010, Mesenchymal migration as a therapeutic target in glioblastoma, J. Oncol., 2010, 10.1155/2010/430142 Cha, 2016, Strategies of mesenchymal invasion of patient-derived brain tumors: microenvironmental adaptation, Sci. Rep., 6, 10.1038/srep24912 Rao, 2003, Molecular mechanisms of glioma invasiveness: the role of proteases, Nat. Rev. Cancer, 3, 489, 10.1038/nrc1121 Farin, 2006, Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis, Glia, 53, 799, 10.1002/glia.20334 Scherer, 1938, Structural development in gliomas, Am. J. Cancer, 34, 333 Pedersen, 1995, Migratory patterns of lac-z transfected human glioma cells in the rat brain, Int. J. Cancer, 62, 767, 10.1002/ijc.2910620620 Zimmermann, 2008, Extracellular matrix of the central nervous system: from neglect to challenge, Histochem. Cell Biol., 130, 635, 10.1007/s00418-008-0485-9 Zhang, 1998, Expression of a cleaved brain-specific extracellular matrix protein mediates glioma cell invasion in vivo, J. Neurosci., 18, 2370, 10.1523/JNEUROSCI.18-07-02370.1998 Xia, 2016, Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation, Neuro Oncol., 18, 507, 10.1093/neuonc/nov171 Valster, 2005, Cell migration and invasion assays, Methods, 37, 208, 10.1016/j.ymeth.2005.08.001 Justus, 2014, In vitro cell migration and invasion assays, J. Vis. Exp., 88 Friedl, 2012, New dimensions in cell migration, Nat. Rev. Mol. Cell Biol., 13, 743, 10.1038/nrm3459 Levin, 2012, Protein and phosphoprotein levels in glioma and adenocarcinoma cell lines grown in normoxia and hypoxia in monolayer and three-dimensional cultures, Proteome Sci., 10, 5, 10.1186/1477-5956-10-5 Heffernan, 2015, Bioengineered scaffolds for 3D analysis of glioblastoma proliferation and invasion, Ann. Biomed. Eng., 43, 1965, 10.1007/s10439-014-1223-1 Thomas, 2000, Spreading and motility of human glioblastoma cells on sheets of silicone rubber depend on substratum compliance, Med. Biol. Eng. Comput., 38, 360, 10.1007/BF02347059 David, 2004, Reticulated hyaluronan hydrogels: a model for examining cancer cell invasion in 3D, Matrix Biol., 23, 183, 10.1016/j.matbio.2004.05.005 Rao, 2013, Glioblastoma behaviors in three-dimensional collagen-hyaluronan composite hydrogels, ACS Appl. Mater. Interfaces, 5, 9276, 10.1021/am402097j Yang, 2011, Influence of chondroitin sulfate and hyaluronic acid on structure, mechanical properties, and glioma invasion of collagen I gels, Biomaterials, 32, 7932, 10.1016/j.biomaterials.2011.07.018 Wang, 2013, Astrocytes directly influence tumor cell invasion and metastasis in vivo, PLoS One, 8 Coniglio, 2013, Review: molecular mechanism of microglia stimulated glioblastoma invasion, Matrix Biol., 32, 372, 10.1016/j.matbio.2013.07.008 Chonan, 2017, Endothelium-induced three-dimensional invasion of heterogeneous glioma initiating cells in a microfluidic coculture platform, Integr. Biol. (Camb.), 9, 762, 10.1039/C7IB00091J Fernandes, 2016, A novel microfluidic cell co-culture platform for the study of the molecular mechanisms of Parkinson’s disease and other synucleinopathies, Front. Neurosci., 10, 10.3389/fnins.2016.00511 Gao, 2011, A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology, Biomed. Microdevices, 13, 539, 10.1007/s10544-011-9523-9 Ogawa, 2018, Glioblastoma model using human cerebral organoids, Cell Rep., 23, 1220, 10.1016/j.celrep.2018.03.105 Jung, 2002, Brain tumor invasion model system using organotypic brain-slice culture as an alternative to in vivo model, J. Cancer Res. Clin. Oncol., 128, 469, 10.1007/s00432-002-0366-x Jung, 2001, Tracking the invasiveness of human astrocytoma cells by using green fluorescent protein in an organotypical brain slice model, J. Neurosurg., 94, 80, 10.3171/jns.2001.94.1.0080 Yoshida, 2002, Tracking cell invasion of human glioma cells and suppression by anti-matrix metalloproteinase agent in rodent brain-slice model, Brain Tumor Pathol., 19, 69, 10.1007/BF02478930 Ohnishi, 1998, A novel model of glioma cell invasion using organotypic brain slice culture, Cancer Res., 58, 2935 Jensen, 2016, Establishment and characterization of a tumor stem cell-based glioblastoma invasion model, PLoS One, 11, 10.1371/journal.pone.0159746 Holtkamp, 2005, Brain slice invasion model reveals genes differentially regulated in glioma invasion, Biochem. Biophys. Res. Commun., 336, 1227, 10.1016/j.bbrc.2005.08.253 Yamada, 2007, Modeling tissue morphogenesis and cancer in 3D, Cell, 130, 601, 10.1016/j.cell.2007.08.006 Moser, 2003, Brain capillaries and cholinergic neurons persist in organotypic brain slices in the absence of blood flow, Eur. J. Neurosci., 18, 85, 10.1046/j.1460-9568.2003.02728.x Hutter-Schmid, 2015, Organotypic brain slice cultures as a model to study angiogenesis of brain vessels, Front. Cell Dev. Biol., 3, 52, 10.3389/fcell.2015.00052 Guillamo, 2001, Migration pathways of human glioblastoma cells xenografted into the immunosuppressed rat brain, J. Neurooncol., 52, 205, 10.1023/A:1010620420241 Yoshida, 2004, Inhibition of glioma angiogenesis and invasion by SI-27, an anti-matrix metalloproteinase agent in a rat brain tumor odel, Neurosurgery, 54, 1213, 10.1227/01.NEU.0000119237.46690.C6 Sampetrean, 2011, Invasion precedes tumor mass formation in a malignant brain tumor model of genetically modified neural stem cells, Neoplasia, 13, 784, 10.1593/neo.11624 Zhang, 2011, In vivo MRI tracking of cell invasion and migration in a rat glioma model, Mol. Imaging Biol., 13, 695, 10.1007/s11307-010-0401-2 Ricard, 2014, Six-color intravital two-photon imaging of brain tumors and their dynamic microenvironment, Front. Cell. Neurosci., 8, 57, 10.3389/fncel.2014.00057 Pittet Mikael, 2011, Intravital Imaging, Cell, 147, 983, 10.1016/j.cell.2011.11.004 Joo, 2013, Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ, Cell Rep., 3, 260, 10.1016/j.celrep.2012.12.013